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Mixed protein-DNA gel particles for DNA delivery: Role of protein composition and preparation method on biocompatibility

Moran, M. C.; Nogueira, D. R.; Vinardell, M. P.; Miguel, M. G. and Lindman, Björn LU (2013) In International Journal of Pharmaceutics 454(1). p.192-203
Abstract
Mixtures of two cationic proteins were used to prepare protein-DNA gel particles, employing associative phase separation and interfacial diffusion (Moran et al., 2009a). By mixing the two proteins, we have obtained particles that displayed higher loading efficiency and loading capacity values than those obtained in single-protein systems. However, nothing is known about the adverse effects on haemocompatibility and cytotoxicity of these protein-DNA gel particles. Here, we examined the interaction of protein-DNA gel particles obtained by two different preparation methods, and their components, with red blood cells and established cells. From a haemolytic point of view, these protein-DNA gel particles were demonstrated to be promising... (More)
Mixtures of two cationic proteins were used to prepare protein-DNA gel particles, employing associative phase separation and interfacial diffusion (Moran et al., 2009a). By mixing the two proteins, we have obtained particles that displayed higher loading efficiency and loading capacity values than those obtained in single-protein systems. However, nothing is known about the adverse effects on haemocompatibility and cytotoxicity of these protein-DNA gel particles. Here, we examined the interaction of protein-DNA gel particles obtained by two different preparation methods, and their components, with red blood cells and established cells. From a haemolytic point of view, these protein-DNA gel particles were demonstrated to be promising long-term blood-contacting medical devices. Safety evaluation with the established cell lines revealed that, in comparison with proteins in solution, the cytotoxicity was reduced when administered in the protein-DNA systems. In comparison with large-sized particles, the cytotoxic responses of small-sized protein-DNA gel particles showed to be strongly dependent of both the protein composition and the cell line being the tumour cell line HeLa more sensitive to the deleterious effects of the mixed protein-based particles. The observed trends in haemolysis and cell viabilities were in agreement with the degree of complexation values obtained for the protein-DNA gel particles prepared by both preparation methods. (c) 2013 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
DNA gels, Particles, Size, Haemolysis, In vitro cytotoxicity
in
International Journal of Pharmaceutics
volume
454
issue
1
pages
192 - 203
publisher
Elsevier
external identifiers
  • wos:000323854600024
  • scopus:84884158218
ISSN
1873-3476
DOI
10.1016/j.ijpharm.2013.06.041
language
English
LU publication?
yes
id
94a0244c-8288-4204-bc82-5dfd473877e9 (old id 4106525)
date added to LUP
2013-11-05 13:49:31
date last changed
2019-02-20 03:04:37
@article{94a0244c-8288-4204-bc82-5dfd473877e9,
  abstract     = {Mixtures of two cationic proteins were used to prepare protein-DNA gel particles, employing associative phase separation and interfacial diffusion (Moran et al., 2009a). By mixing the two proteins, we have obtained particles that displayed higher loading efficiency and loading capacity values than those obtained in single-protein systems. However, nothing is known about the adverse effects on haemocompatibility and cytotoxicity of these protein-DNA gel particles. Here, we examined the interaction of protein-DNA gel particles obtained by two different preparation methods, and their components, with red blood cells and established cells. From a haemolytic point of view, these protein-DNA gel particles were demonstrated to be promising long-term blood-contacting medical devices. Safety evaluation with the established cell lines revealed that, in comparison with proteins in solution, the cytotoxicity was reduced when administered in the protein-DNA systems. In comparison with large-sized particles, the cytotoxic responses of small-sized protein-DNA gel particles showed to be strongly dependent of both the protein composition and the cell line being the tumour cell line HeLa more sensitive to the deleterious effects of the mixed protein-based particles. The observed trends in haemolysis and cell viabilities were in agreement with the degree of complexation values obtained for the protein-DNA gel particles prepared by both preparation methods. (c) 2013 Elsevier B.V. All rights reserved.},
  author       = {Moran, M. C. and Nogueira, D. R. and Vinardell, M. P. and Miguel, M. G. and Lindman, Björn},
  issn         = {1873-3476},
  keyword      = {DNA gels,Particles,Size,Haemolysis,In vitro cytotoxicity},
  language     = {eng},
  number       = {1},
  pages        = {192--203},
  publisher    = {Elsevier},
  series       = {International Journal of Pharmaceutics},
  title        = {Mixed protein-DNA gel particles for DNA delivery: Role of protein composition and preparation method on biocompatibility},
  url          = {http://dx.doi.org/10.1016/j.ijpharm.2013.06.041},
  volume       = {454},
  year         = {2013},
}